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Nitrosothiols regulate antioxidant capacity in red blood cells
Author(s) -
Rogers Stephen Colin,
Corcuera Daniella,
McLaughlin Dylan,
Patel Krupali,
Ross Jerlinda,
Doctor Allan
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.lb130
Subject(s) - glutathione , nicotinamide adenine dinucleotide phosphate , pentose phosphate pathway , chemistry , biochemistry , oxidative stress , thiol , antioxidant , dehydrogenase , glycolysis , glutaredoxin , glutathione reductase , superoxide , reactive oxygen species , glyceraldehyde 3 phosphate dehydrogenase , cysteine , oxidative phosphorylation , enzyme , glutathione peroxidase , oxidase test
Hypoxic RBCs are less resilient to oxidative stress. This results from constrained glycolytic flux through the hexose monophosphate pathway (HMP), the RBCs sole source of nicotinamide adenine dinucleotide phosphate (NADPH). NADPH plays an essential role in maintaining thiol‐based anti‐oxidant defense by regenerating glutathione (GSH) from the glutathione disulphide. We hypothesized that pre‐exposure of RBCs to exogenous nitrosothiol would recover thiol‐based oxidant defence under hypoxic conditions by inhibiting the EMP enzyme glyceraldehyde 3‐phosphate dehydrogenase and enhacing HMP glycolytic flux. Human erythrocytes pre‐incubated ± L‐cysteine NO (L‐CysNO; SNO:Hb 1:250) under oxygenated conditions, were subjected to controlled oxidant (superoxide) loading following hypoxic exposure. The sufficiency of antioxidant defense was determined by measurement of reduced RBC membrane thiol and serial quantification of GSH and NADPH redox couples. The loss of reduction potential and reduced membrane thiol observed in control hypoxic RBCs was restored in the L‐CysNO pre‐treated hypoxic RBCs. These data indicate that nitrosothiols may abrogate hypoxia‐induced vulnerability to oxidative stress.